title: MicroRNA-31 inhibits cisplatin-induced apoptosis in non-small cell lung cancer cells by regulating the drug transporter ABCB9.
abstract: Alterations in microRNA (miRNA) expression have been found to be involved in tumor growth and response to chemotherapy. However, the possible role of miR-31 in cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC) remains unclear. In this study, we identified a DDP-sensitive and a DDP-resistant cell line from four candidate human NSCLC cell lines. Notably, we found that miR-31 was significantly upregulated in the DDP-resistant cell line compared with its level in the DDP-sensitive cell line. As a result, miR-31 overexpression induced DDP resistance in the DDP-sensitive cell line, and miR-31 knockdown rescued DDP sensitivity in the DDP-resistant cell line. Interestingly, miR-31 was inversely correlated with the expression of the drug resistance gene ABCB9. The luciferase activity assay showed that miR-31 directly targets the 3'UTR of ABCB9, which is known to play a crucial role in drug resistance. Mechanistically, we showed that miR-31 confers DDP-induced apoptosis and that inhibition of ABCB9 is required for DDP resistance. The data demonstrate that miR-31 exerts an anti-apoptotic effect most likely through the inhibition of ABCB9 and thus provide a novel strategy involving the use of miR-31 as a potential target in NSCLC chemotherapy.
authors.affiliation: Institute of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Institute of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Institute of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Oncology, The Affiliated Hospital of Ningbo University School of Medicine, Ningbo, China.
authors.forename: Shaomin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China. Electronic address: zhaohui@ncri.org.cn.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Gong
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy; D035683:MicroRNAs / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C412573:ABCB9 protein, human; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin
keywords: ABCB9; Apoptosis; Cisplatin resistance; Non-small cell lung cancer; miR-31